Combination of Carmustine and Selenite Inhibits EGFR Mediated Growth Signaling in Androgen-Independent Prostate Cancer Cells.

Although aberrant androgen receptor (AR) signaling is a central mechanism for castration resistant prostate cancer (CRPC) progression, AR-independent growth signaling is also present in CRPC. The current therapeutic options for patients with CRPC are limited and new drugs are desperately needed to eliminate these crucial growth signaling pathways. We have previously shown that combination of carmustine and selenite effectively induces apoptosis and growth inhibition by targeting AR and AR-variants in CRPC cells.

Combination of carmustine and selenite effectively inhibits tumor growth by targeting androgen receptor, androgen receptor-variants, and Akt in preclinical models: New hope for patients with castration resistant prostate cancer.

Despite established androgen receptor (AR) antagonists, AR/AR-variants signaling remain a major obstacle for the successful treatment of castration resistant prostate cancer (CRPC). In addition, CRPC cells adapt to survive via AR-independent pathways to escape next generation therapies. Therefore, there is an urgent need for drugs that can target these signaling pathways in CRPC.

Oxalate at physiological urine concentrations induces oxidative injury in renal epithelial cells: effect of α-tocopherol and ascorbic acid.

Objectives: To test our hypothesis that physiological levels of urinary oxalate induce oxidative renal cell injury, as studies to date have shown that oxalate causes oxidative injury only at supra-physiological levels. To study the combined effect of α-tocopherol and ascorbic acid against oxalate-induced oxidative injury, as oxalate-induced oxidative cell injury is known to promote initial attachment of calcium oxalate crystals to injured renal tubules and subsequent development of kidney stones.

Materials And Methods: Cultures of normal (antioxidant-undepleted) and antioxidant-depleted LLC-PK1 cells were exposed to oxalate at human physiological urine concentrations.

Carmustine enhances the anticancer activity of selenite in androgen-independent prostate cancer cells.

Apoptosis is one of the major mechanisms targeted in the development of therapies against various cancers, including prostate cancer. Resistance to chemotherapy poses a significant problem for the effective treatment of androgen-independent (hormone-refractory) prostate cancer. Although high concentrations of sodium selenite exert strong anticarcinogenic effects in several cell culture systems and animal models, the therapeutic potential of selenite in patients with advanced or metastatic prostate cancer is extremely limited by the genotoxicity of high-dose selenite.

Selective Rac1 inhibition protects renal tubular epithelial cells from oxalate-induced NADPH oxidase-mediated oxidative cell injury.

Oxalate-induced oxidative cell injury is one of the major mechanisms implicated in calcium oxalate nucleation, aggregation and growth of kidney stones. We previously demonstrated that oxalate-induced NADPH oxidase-derived free radicals play a significant role in renal injury. Since NADPH oxidase activation requires several regulatory proteins, the primary goal of this study was to characterize the role of Rac GTPase in oxalate-induced NADPH oxidase-mediated oxidative injury in renal epithelial cells.

Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 β/β-catenin pathway.

Activation of survival pathways has been associated with chemoresistance and progression of androgen independence which places a major obstacle to successful treatment of metastatic prostate cancer. Deguelin, a rotenoid isolated from Mundulea sericea, has an anticancer effect against several types of cancers; however, the mechanism of its antitumor effects on prostate cancer is not well understood. The aim of our study was to elucidate the effect of deguelin on the growth of prostate cancer cells and its putative mechanism of action.

Oxalate-induced activation of PKC-alpha and -delta regulates NADPH oxidase-mediated oxidative injury in renal tubular epithelial cells.

Oxalate-induced oxidative stress contributes to cell injury and promotes renal deposition of calcium oxalate crystals. However, we do not know how oxalate stimulates reactive oxygen species (ROS) in renal tubular epithelial cells. We investigated the signaling mechanism of oxalate-induced ROS formation in these cells and found that oxalate significantly increased membrane-associated protein kinase C (PKC) activity while at the same time lowering cytosolic PKC activity.

A critical analysis of the role of gut Oxalobacter formigenes in oxalate stone disease.

Hyperoxaluria is a major risk factor for the formation of calcium oxalate stones, but dietary restriction of oxalate intake might not be a reliable approach to prevent recurrence of stones. Hence, other approaches to reduce urinary oxalate to manage stone disease have been explored. The gut-dwelling obligate anaerobe Oxalobacter formigenes (OF) has attracted attention for its oxalate-degrading property.

Vitamin E therapy prevents hyperoxaluria-induced calcium oxalate crystal deposition in the kidney by improving renal tissue antioxidant status.

Objective: To determine whether vitamin E prevents hyperoxaluria-induced stone formation, using a new animal model of calcium oxalate stone disease, as our previous in- vitro and in-vivo studies showed that oxalate and hyperoxaluria induce free-radical generation, which results in peroxidative injury to renal tubular cells.

Materials And Methods: Ethylene glycol (EG) was administered at 150 mg/day by gavage for 3 weeks to rats fed on diets with adequate (group 1), excess (group 2) or deficient (group 3) vitamin E. Several indicators of peroxidation, free radicals and enzymatic activity were then assessed.

Molecular mechanism of oxalate-induced free radical production and glutathione redox imbalance in renal epithelial cells: effect of antioxidants.

Background: Peroxidation of renal cells is a critical event in the nucleation and formation of calcium oxalate crystals under hyperoxaluric conditions. We previously demonstrated that oxalate-induced peroxidative injury is one of the major mechanisms in promoting crystal attachment to renal epithelial cells.

Methods: In this study we have demonstrated that the mechanism of oxalate-induced peroxidative injury is through the induction of TGF-beta1 and glutathione (GSH) redox imbalance in LLC-PK1 cells.

Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants.

In a previous study we demonstrated that oxalate induced free radical injury can promote calcium oxalate stone formation. In the present study, we tested whether the antioxidants vitamin E, superoxide dismutase (SOD), catalase and desferoxamine (DFO) can provide protection against oxalate toxicity in LLC-PK(1) cells. LLC-PK(1) cells were exposed to oxalate (1.